Effects of GCN5L1 on inflammatory injury and Treg cell infiltration in myocardial tissue after myocardial infarction
10.13431/j.cnki.immunol.j.20250023
- VernacularTitle:GCN5L1对心肌梗死后心肌组织中炎性损伤及Treg细胞浸润的影响
- Author:
Wenmei QI
1
;
Honghu WANG
Author Information
1. 054000,邢台市第三医院急诊科
- Publication Type:Journal Article
- Keywords:
Myocardial infarction;
Treg cell;
GCN5L1;
Inflammatory factor
- From:
Immunological Journal
2025;41(3):157-164
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of lysosome biogenesis complex 1 subunit 1(GCN5L1)on myocardial inflammatory injury and regulatory T cell(Treg)infiltration in mice with myocardial infarction(MI).Methods The differentially expressed gene GCN5L1 was screened from the GSE66360 dataset using whole blood samples from healthy controls and MI patients.The correlation between GCN5L1 and IL-10,IL-35 or Treg marker FOXP3 was analyzed.A model of MI was established in C57BL/6 mice by left anterior descending coronary artery ligation.Thirty mice were divided into five groups:sham,MI model,AAV9-NC(control adeno-associated virus),AAV9-GCN5L1 and AAV9-GCN5L1+FOXP3 inhibitor(epirubicin)groups,with 6 mice in each group.MI area was assessed by TTC staining,and histopathological changes were evaluated via HE staining.Immunofluorescence was used to quantify GCN5L1 and FOXP3 positivity;ELISA was used to measure IL-10 and IL-35 levels;Western blot was used to analyze the levels of GCN5L1,Bax,Bcl-2 and PI3K/AKT pathway proteins;transcriptomic sequencing was performed on AAV9-NC and AAV9-GCN5L1 groups,while differential genes subjected to GO and KEGG enrichment analysis.Results GSE66360 dataset showed that GCN5L1 levels were significantly lower in MI patients than in healthy controls,and positively correlated with IL-10,IL-35 and FOXP3 levels(P＜0.01).Compared to the sham group,the MI group exhibited increased infarct area,severe histopathology,reduced GCN5L1/IL-10/IL-35 levels,elevated Bax,and decreased Bcl-2,which could be reversed by AAV9-GCN5L1(P＜0.01).Transcriptomics revealed the enrichment of differential genes in Treg infiltration and PI3K/AKT pathways.The AAV9-GCN5L1 group showed higher FOXP3 positivity and PI3K/AKT expression than the MI group.Co-treatment with AAV9-GCN5L1+epirubicin reduced FOXP3 positivity compared to AAV9-GCN5L1 alone(P＜0.01).Conclusion GCN5L1 overexpression alleviates myocardial inflammatory injury post-MI,activates the PI3K/AKT pathway,and enhances Treg infiltration.
